Oligogenic inheritance of a human heart disease involving a genetic modifier.

Complex genetic mechanisms are thought to underlie many human diseases, yet experimental proof of this model has been elusive. Here, we show that a human cardiac anomaly can be caused by a combination of rare, inherited heterozygous mutations. Whole-exome sequencing of a nuclear family revealed that three offspring with childhood-onset cardiomyopathy had inherited three missense single-nucleotide variants in the , , and genes.

Prominent coronary artery flow with normal coronary artery anatomy is a rare but ominous harbinger of poor outcome in the fetus.

Objectives: "Heart sparing" refers to prominent antegrade fetal coronary artery (CA) blood flow readily visualized by color Doppler and is a harbinger of poor outcome in growth restricted fetus, but little is known of the features and presentation of heart sparing in normally grown fetuses. Our objective was to describe heart sparing effects in normally grown fetuses, and compare the presentation and outcome of heart sparing between fetuses with growth restriction and those who were normally grown.

Methods: In a series of fetuses with prominent antegrade CA flow, we assessed Doppler flow profiles in the aortic isthmus, ductus venosus (DV), umbilical vein (UV), umbilical artery (UA) and middle cerebral artery (MCA).

Tissue Doppler is more sensitive and reproducible than spectral pulsed-wave Doppler for fetal right ventricle myocardial performance index determination in normal and diabetic pregnancies.

Background: The aim of this study was to compare the reproducibility, agreement, and sensitivity of pulsed-wave Doppler tissue imaging (DTI) versus spectral Doppler assessment of right ventricular (RV) myocardial performance index (MPI) in midgestation fetuses in both a normal and a disease state.

Methods: RV MPI was calculated using pulsed-wave DTI and spectral Doppler in normal pregnancies (n = 69) and in women with pregestational diabetes (n = 51). Intraobserver and interobserver variability and agreement were evaluated using Bland-Altman analysis.

Danon disease with typical early-onset cardiomyopathy in a male: focus on a novel LAMP-2 mutation.

We report a case of a 16-yr-old male with Danon disease caused by a novel mutation in the LAMP-2 gene. Mutations in the LAMP-2 gene result in the absence of LAMP-2 on immunohistochemical staining of muscle tissue, thus defining Danon disease, a rare X-linked myopathy. It is characterized clinically by HCM or left ventricular hypertrophy, a WPW pattern on ECG, variable degrees of muscular weakness (skeletal myopathy), mental retardation, and retinal changes.

Phospholipase Cepsilon regulates ovulation in Caenorhabditis elegans.

Phospholipase Cepsilon (PLCepsilon) is a novel class of phosphoinositide-specific PLC with unknown physiological functions. Here, we present the first genetic analysis of PLCepsilon in an intact organism, the nematode Caenorhabditis elegans. Ovulation in C.

Caenorhabditis elegans inositol 5-phosphatase homolog negatively regulates inositol 1,4,5-triphosphate signaling in ovulation.

Ovulation in Caenorhabditis elegans requires inositol 1,4,5-triphosphate (IP(3)) signaling activated by the epidermal growth factor (EGF)-receptor homolog LET-23. We generated a deletion mutant of a type I 5-phosphatase, ipp-5, and found a novel ovulation phenotype whereby the spermatheca hyperextends to engulf two oocytes per ovulation cycle. The temporal and spatial expression of IPP-5 is consistent with its proposed inhibition of IP(3) signaling in the adult spermatheca.